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We are analyzing https://www.nature.com/articles/6691796.

Title:
Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials | British Journal of Cancer
Description:
British Journal of Cancer - Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Keywords {πŸ”}

cancer, google, scholar, article, activity, drug, nature, vivo, models, hollow, fibre, tumor, cas, preclinical, development, vitro, compounds, content, tested, human, cell, anticancer, cookies, journal, open, clinical, trials, xenograft, screening, practice, oncology, privacy, data, access, national, agents, correlation, assay, intraperitoneal, response, research, devita, hellmann, rosenberg, principles, lippincottraven, philadelphia, analysis, british, nci,

Topics {βœ’οΈ}

nature portfolio medicinal chemistry libraries nature privacy policy advertising social media 0/ reprints anticancer drug development pharmaceutical policy permissions personal data xenograft data preclinical drug development hollow fiber assay animal models utilized phase ii trials data protection cancer drug discovery cancer chemotherapeutic agents vitro antitumor screen privacy developmental therapeutics program hollow fibre responses molecular docking studies hollow fibre assay hollow fibre activity journals search log explore content early clinical trials tumor panel screening subcutaneous activity combined tumor development national cancer institute' human cancer histology national cancer institute anti-cancer effect european economic area 4h-chromen-7-yl ]quinoline-based heterocycles knowledge-based approach americal chemical society ox40 agonist alexander accepting optional cookies microculture tetrazolium assay anti-proliferative activity finding xenograft activity vivo tumour models hydrogen-bonding factors pre-clinical models antitumor drugs

Schema {πŸ—ΊοΈ}

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         headline:Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials
         description:An analysis of the activity of compounds tested in pre-clinical in vivo and in vitro assays by the National Cancer Institute's Developmental Therapeutics Program was performed. For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. However, for compounds with in vivo activity in at least one-third of tested xenograft models, there was correlation with ultimate activity in at least some Phase II trials. Thus, an efficient means of predicting activity in vivo models remains desirable for compounds with anti-proliferative activity in vitro. For 564 compounds tested in the hollow fibre assay which were also tested against in vivo tumour models, the likelihood of finding xenograft activity in at least one-third of the in vivo models tested rose with increasing intraperitoneal hollow fibre activity, from 8% for all compounds tested to 20% in agents with evidence of response in more than 6 intraperitoneal fibres (P< 0.0001). Intraperitoneal hollow fibre activity was also found to be a better predictor of xenograft activity than either subcutaneous hollow fibre activity or intraperitoneal plus subcutaneous activity combined. Since hollow fibre activity was a useful indicator of potential in vivo response, correlates with hollow fibre activity were examined for 2304 compounds tested in both the NCI 60 cell line in vitro cancer drug screen and hollow fibre assay. A positive correlation was found for histologic selectivity between in vitro and hollow fibre responses. The most striking correlation was between potency in the 60 cell line screen and hollow fibre activity; 56% of compounds with mean 50% growth inhibition below 10Ҁ“7.5 M were active in more than 6 intraperitoneal fibres whereas only 4% of compounds with a potency of 10Ҁ“4 M achieved the same level of hollow fibre activity (P< 0.0001). Structural parameters of the drugs analysed included compound molecular weight and hydrogen-bonding factors, both of which were found to be predictive of hollow fibre activity. © 2001 Cancer Research Campaign
         datePublished:2001-05-15T00:00:00Z
         dateModified:2011-11-16T00:00:00Z
         pageStart:1424
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            in vitro-to-in vivo correlations
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            Epidemiology
            Molecular Medicine
            Oncology
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      headline:Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials
      description:An analysis of the activity of compounds tested in pre-clinical in vivo and in vitro assays by the National Cancer Institute's Developmental Therapeutics Program was performed. For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. However, for compounds with in vivo activity in at least one-third of tested xenograft models, there was correlation with ultimate activity in at least some Phase II trials. Thus, an efficient means of predicting activity in vivo models remains desirable for compounds with anti-proliferative activity in vitro. For 564 compounds tested in the hollow fibre assay which were also tested against in vivo tumour models, the likelihood of finding xenograft activity in at least one-third of the in vivo models tested rose with increasing intraperitoneal hollow fibre activity, from 8% for all compounds tested to 20% in agents with evidence of response in more than 6 intraperitoneal fibres (P< 0.0001). Intraperitoneal hollow fibre activity was also found to be a better predictor of xenograft activity than either subcutaneous hollow fibre activity or intraperitoneal plus subcutaneous activity combined. Since hollow fibre activity was a useful indicator of potential in vivo response, correlates with hollow fibre activity were examined for 2304 compounds tested in both the NCI 60 cell line in vitro cancer drug screen and hollow fibre assay. A positive correlation was found for histologic selectivity between in vitro and hollow fibre responses. The most striking correlation was between potency in the 60 cell line screen and hollow fibre activity; 56% of compounds with mean 50% growth inhibition below 10Ҁ“7.5 M were active in more than 6 intraperitoneal fibres whereas only 4% of compounds with a potency of 10Ҁ“4 M achieved the same level of hollow fibre activity (P< 0.0001). Structural parameters of the drugs analysed included compound molecular weight and hydrogen-bonding factors, both of which were found to be predictive of hollow fibre activity. © 2001 Cancer Research Campaign
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      dateModified:2011-11-16T00:00:00Z
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         anticancer drug discovery
         in vitro-to-in vivo correlations
         clinical trials
         Biomedicine
         general
         Cancer Research
         Epidemiology
         Molecular Medicine
         Oncology
         Drug Resistance
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      name:SAIC-Frederick, Frederick
      name:SAIC-Frederick, Frederick
      name:Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda
      name:Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda
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